From: On the predictive utility of animal models of osteoarthritis
Trial | Target | Disease modification | Symptomatic outcome (secondary endpoint) | Preclinical validation in OA model | Structural outcome | Symptomatic outcome |
---|---|---|---|---|---|---|
Oral salmon calcitonin (n = 1,176 and n = 1,030; 2 years) [145] | SCB | JSW: no effect. No statistically significant effect on biochemical markers of bone (CTX-I) and cartilage degradation (CTX-II) | WOMAC: no statistically significant effect | Rat MNX and MNX/OVX [146]: 8 weeks, treatment at start | Joint protection, serum CTX-II ↓ | NA |
 |  |  |  | Dog ACLT: Rx at surgery, 84 days (nasal delivery) [147] | Joint protection (no effect on osteophytes) | NA |
 |  |  |  | DMM in mice overexpressing salmon calcitonin [148] | OARSI score ↓ 7 weeks after DMM | NA |
Intra-articular rFGF18 (n = 168; 12 months) [149] | Cartilage (anabolic) | Primary endpoint, (reduction of cartilage loss in the central medial femorotibial compartment on MRI) not met. Secondary structural endpoints were met | WOMAC: improved | Rat MMT: 6 weeks; Rx start week 3 [150] | Increased thickness of the articular surface of the medial tibial plateau. Reduced degeneration scores | NA |
Strontium ranelate (n = 1,371; 3 years) [151] | SCB | JSW: fewer radiographic progressors (both low and high dose) | Beneficial effects on symptoms (high dose only) | Dog ACLT [152]: 16 weeks; Rx start week 4 | Cartilage lesions ↓ (macrosc/histol), SCB thickening ↓ (histomorphometry), serum CTXII ↓ | NA |
 |  |  |  | Rat MMT [153]: 3 or 6 weeks; Rx start at surgery | Cartilage degeneration ↓, SCB remodeling ↓ | NA |
SD6010, oral selective iNOS inhibitor (n = 1,048; 2 years) [154] | Cartilage | JSW: no effect | No effect on pain or function | Cartilage lesions ↓ (macrosc/histol), osteophytes ↓, synovial inflammation ↓ | NA | |
 |  |  |  | Collagenase induced arthritis in Nos2 null mice [157] | Cartilage proteoglycan loss ↓, cartilage lesions ↓, osteophytes ↓ | NA |
 |  |  |  | Rat MMT model [158] | NA | Reversal of mechanical allodynia and reversal of WBD 3 hours after drug administration |
Zoledronic acid (n = 59; single infusion; 6 and12 month follow-up) [77] | SCB | MRI BML area: reduction in total BML area significant at 6 but not 12 months | VAS pain scores ↓ at 6 months, but not KOOS |  |  | |
 |  |  |  | a) prophylactic | Joint preservation | Reversal of WBD |
 |  |  |  | b) therapeutic (early or late intervention) | Partial preservation, diminishes with late intervention | Partial effect, diminishing with late intervention |
Vitamin D3 (n = 146; 2 years) [159] | SCB cartilage | MRI cartilage volume: no effect | WOMAC: no effect | Rat pMNX [160]: prophylactic; 40 days | Inconclusive | NA |
 |  |  |  | Osteochondrosis/OA in pigs; Vit D3 in diet [161] | No effect on OA incidence or severity of OA lesions, or cartilage biochemistry | NA |
Licofelone (5-LOX and COX inhibitor; n = 355; 2 years; not placebo controlled but compared with NSAID) [162] | Inflammation | JSW: no effect | WOMAC: pain improved | Dog ACLT [163]: 12 weeks; Rx start week 4 | MRI cartilage volume ↑, cartilage damage and osteophytes ↓(macroscopic evaluation only) | NA |
Risedronate | SCB |  |  | DH guinea pig [164]: up to 24 weeks | OARSI score: no effect. Serum CTX-II ↓ | NA |
 |  |  |  | NZW rabbits ACLT [165]: 11 weeks; Rx start week 3 | Loss of cartilage ↓, SCB damage ↓, serum CTX-II ↓ | NA |
N = 284 (1 year) [166] |  | JSW: trend toward improvement. Cartilage degradation and bone resorption markers ↓ | WOMAC ↓ |  |  |  |
N = 2,483 (2 years) [167] |  | JSW: no effect. uCTXII ↓ | WOMAC : no effect |  |  |  |
N =1,232 (2Â years) [168] | Â | Preserved SCB integrity | NA | Â | Â | Â |
Broad-spectrum MMP inhibitor (n =401; 1 year) [169] | Cartilage | JSW: no effect | No effect on pain | rat MIA [170]: 3 weeks; Rx during first week | Cartilage damage ↓ | NA |
 |  |  |  | STR/Ort mice [171]: 12 weeks | Improved radiographic score and less cartilage and bone damage | NA |
Doxycycline (n = 403; 30 months) [172] | Cartilage | JSW: slowed JSN in ipsilateral knee | No effect on pain | Dog ACLT (after dorsal root ganglionectomy) [173]: 8 weeks; Rx at start | Less damage on femoral condyle. No effect on tibial plateau or osteophytes | NA |
 |  |  |  | DH guinea pig [174]: 9 months old; 66 days | Less cartilage volume loss (MRI) | NA |
 |  |  |  | DMM (mouse) [175]: 4 weeks; Rx at start | Less cartilage loss | NA |